Sarcopenia, defined as age related loss of muscle mass and muscle function and strength, is very prevalent among the elderly. Sarcopenia is one of the largest public health problems facing a rapidly increasing, aging population in the United States and leads to increased incidence of falls, fractures and associated morbidities. Previous observations from our laboratory, as well as from many other laboratories, have demonstrated the efficacy of 2-hydroxy-2-methylbutyrate (HMB) alone or in combination with other amino acids in enhancing muscle strength and function in young athletes. We have recently demonstrated that the combination of HMB with two other amino acids, arginine and lysine, was effective in increasing muscle mass in elderly men and women during a year-long prospective study. When analyzing the data (Preliminary Results), we demonstrated a close correlation between the levels of 25-OH Vitamin D3 in this population and the level of improvement in muscle strength. We noted that individuals with plasma 25-OH Vitamin D3 levels >30 ng/ml manifested muscle strength gains supplemented with HMB and two amino acids, while those with plasma 25- OH Vitamin D3 of <30 ng/ml did not. These data form the basis of our current hypothesis that the combination of HMB and Vitamin D supplementation will be synergistic and will result in significant enhancements in overall muscle strength, function and muscle mass. We propose these Phase I and Phase II studies to prove our hypothesis. The Phase I study will test the short-term (12-wk) efficacy of a combination of HMB and Vitamin D to prevent and reverse muscle sarcopenia and the associated losses of muscular strength and functionality in older adults. We plan to recruit 100 men and women who will be assigned to one of four dietary treatments: (1) Control;(2) HMB (calcium salt), 3.0 g/day;(3) 2,000 IU Vitamin D;and (4) HMB, 3.0 g/d + 2,000 IU Vitamin D. The subjects will undergo a 3-day per week exercise program, and body composition and strength will be measured at four week intervals. We expect to demonstrate the synergy between HMB and Vitamin D in this short study. Phase II will test the long-term (12-mos) efficacy of this synergistic combination of HMB and Vitamin D on the enhancement of muscle strength and functionality in the elderly, thus leading to improved quality of life. Phase II will include an exercise arm just like Phase I, but will also include a non-exercise arm because many elderly adults do not participate in an exercise program. In addition to body composition and function and strength data, muscle biopsies will be obtained and muscle fiber and proteomic analysis will be performed. We anticipate that the data generated will lead to further research looking at mechanism(s) involved in loss of muscle and muscle function in the elderly. Improvement in muscle strength and muscle function as well as improvements in body composition over the year-long study will be used to market a product containing HMB and Vitamin D. PUBLIC HEALTH RELEVANCE: Current estimates place a large portion of the older U.S. populous at risk for falls with potential morbidities. A large percentage of these falls are directly related to decreased muscle strength and function. Since a significant portion of the older population is at risk of having a Vitamin D deficiency, a product that corrects such deficiencies and specifically targets muscle strength, function, and mass is likely to produce significant improvements in health, improve the quality of life, and in particular, help to decrease the incidence of falls and injury in this group. Moreover, based upon the incidence of widespread Vitamin D deficiency in all ages, we anticipate the younger population will also benefit from similar supplementation.